title: Prepubertal children with growth hormone deficiency treated for four years with growth hormone experience dose-dependent increase in height, but not in the rate of puberty initiation.
abstract: OBJECTIVE
  Limited data exist on long-term dose response to recombinant human growth hormone (rhGH) in prepubertal GH-deficient (GHD) children. The effect of low, intermediate, and high-dose rhGH (25, 50, and 100 μg/kg/day, respectively) on growth and puberty in children with GHD was investigated for 48 months.
  
  
  METHODS
  A prospective, dose-response study in 111 patients (aged 3-16 years) evaluated growth velocity (cm/year), height standard deviation score (HSDS), corrected HSDS, bone age/chronologic age ratio, body mass index SDS, and the percentage starting puberty.
  
  
  RESULTS
  Dose-related increases were observed in growth velocity (p < 0.001), HSDS (p < 0.001), and corrected HSDS (p < 0.001) from baseline to 48 months. Increases in the bone age/chronologic age ratio (p = 0.043) and body mass index SDS (p = 0.018) occurred up to 36 months at intermediate and high doses versus low-dose rhGH; increases at 48 months were not significant. No significant differences in growth were found between intermediate and high doses of rhGH. Percentages of rhGH-treated patients starting puberty at each dose were equivalent (p = 0.607).
  
  
  CONCLUSIONS
  rhGH, 50 and 100 μg/kg/day, induced greater growth than 25 μg/kg/day without altering the proportion of children starting puberty. The maximum approved dose for pubertal patients (100 μg/kg/day) is not required or recommended for prepubertal children with GHD.
authors.affiliation: Department of Pediatrics, University of Virginia Health System, Charlottesville, Va., USA. adrogol@comcast.net
authors.forename: Alan D
authors.initials: AD
authors.lastname: Rogol
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: Wayne
authors.initials: W
authors.lastname: Weng
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Kappelgaard
authors.forename: John A
authors.initials: JA
authors.lastname: Germak
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011627:Puberty / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012741:Sexual Maturation / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone